Sepsis is a leading cause of death in the United States. During sepsis, the body undergoes a severe inflammatory response to infection. Early detection of the blood-borne pathogens underlying the infection remains crucial to preventing the onset of sepsis. Traditional methods of detection and identification of these pathogens often involve the use of antibodies specific for the pathogen of interest in immune-based assays.
Development of antibodies that efficiently and reliably capture particular pathogen species from biological matrices, such as blood, is complicated by the large number of strain types, often with markedly different antigenic properties (serotypes), which can exist within a species. Antibodies raised against a single index strain of species may not cross-react with other isolates, or strains of the same species. Accordingly, the development of an antibody that can be used against a wide variety of strains is problematic.
One possible solution would be to inoculate against all, or nearly all, of the known different strain-types and combine the antibodies. This, however, would require inoculation of hundreds of animals with individual pathogen strains. Combining isolates within the inoculation medium may reduce the number of animals required, however, a large number of animals is still necessary to cover combinations of all the known serotypes.
Another strategy would be to determine the minimal subset of strains that would represent most, or all, of the antigenic variations across a species. For some species, data regarding the known antigenic variation across the species is available, as well as the relative abundance of the antigenic variants, i.e., the serotypes, in different diseases or environments. However, such information does not exist for most species, indicating a need for alternate methods of developing antibodies that can be used across antigenic variants.